NM_001164277.2(SLC37A4):c.936dup (p.Val313fs) AND Glucose-6-phosphate transport defect

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Nov 15, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000807219.7

Allele description [Variation Report for NM_001164277.2(SLC37A4):c.936dup (p.Val313fs)]

NM_001164277.2(SLC37A4):c.936dup (p.Val313fs)

Gene:

SLC37A4:solute carrier family 37 member 4 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

11q23.3

Genomic location:

Preferred name:

NM_001164277.2(SLC37A4):c.936dup (p.Val313fs)

HGVS:

NC_000011.10:g.119026015dup
NG_013331.1:g.9891dup
NM_001164277.2:c.936dupMANE SELECT
NM_001164278.2:c.936dup
NM_001164279.2:c.717dup
NM_001164280.2:c.936dup
NM_001467.6:c.936dup
NP_001157749.1:p.Val313fs
NP_001157749.1:p.Val313fs
NP_001157750.1:p.Val313fs
NP_001157751.1:p.Val240fs
NP_001157752.1:p.Val313fs
NP_001458.1:p.Val313fs
LRG_187t1:c.936dup
LRG_187:g.9891dup
LRG_187p1:p.Val313fs
NC_000011.9:g.118896724_118896725insT
NC_000011.9:g.118896725dup
NM_001164277.1:c.936dup
NM_001164277.2:c.936dupAMANE SELECT
NM_001164278.1:c.936dup

Protein change:

V240fs

Links:

dbSNP: rs782172072

NCBI 1000 Genomes Browser:

rs782172072

Molecular consequence:

NM_001164277.2:c.936dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001164278.2:c.936dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001164279.2:c.717dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001164280.2:c.936dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001467.6:c.936dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Glucose-6-phosphate transport defect (GSD1B)
Synonyms:: Glycogen storage disease type 1B; GSD Ib
Identifiers:: MONDO: MONDO:0009288; MedGen: C0268146; Orphanet: 364; Orphanet: 79259; OMIM: 232220

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000947262	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 16, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9758626, 10940311, 28492532
SCV001424492	Centogene AG - the Rare Disease Company	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004222672	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Nov 15, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 9758626, 33977030 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000947262

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 16, 2018)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001424492

Centogene AG - the Rare Disease Company

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004222672

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Nov 15, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Structural requirements for the stability and microsomal transport activity of the human glucose 6-phosphate transporter.

Chen LY, Lin B, Pan CJ, Hiraiwa H, Chou JY.

J Biol Chem. 2000 Nov 3;275(44):34280-6.

PubMed [citation]

PMID:: 10940311

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000947262.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SLC37A4 are known to be pathogenic (PMID: 9758626, 10940311). This variant has not been reported in the literature in individuals with SLC37A4-related disease. This variant is present in population databases (rs782172072, ExAC 0.009%). This sequence change creates a premature translational stop signal (p.Val313Serfs*13) in the SLC37A4 gene. It is expected to result in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Centogene AG - the Rare Disease Company, SCV001424492.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004222672.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: SLC37A4 c.936dupA (p.Val313SerfsX13) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 8.3e-06 in 241170 control chromosomes. c.936dupA has been reported in the literature in individuals affected with Glycogen Storage Disease Type Ib (example, Veiga_1998, Halligan_1998). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 33977030, 9758626). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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